The predominant resistance mechanism observed in Gram-negative bacteria involves the production of β-lactamases, which catalyse the hydrolysis of β-lactam antibiotics, thereby rendering them ineffective. Although Isoxazolyl Penicillins have been available since the 1970s, there are currently no structures in complex with class-A β-lactamases available. Here we have analysed the structure of the clinically relevant β-lactamase CTX-M-14 from Klebsiella pneumoniae near physiological temperatures, via serial synchrotron crystallography. We demonstrate the acyl-enzyme intermediates of the catalytically impaired CTX-M-14 mutant E166A in complex with three Isoxazolyl-Penicillins: Oxacillin, Cloxacillin and Dicloxacillin. Structural comparisons of CTX-M-Penicillin complexes show that, while conserved active-site interactions are maintained, each Isoxazolyl-Penicillin adopts a distinct conformation. While the three derivatives differ only by one and two chlorine atoms, respectively, their conformational heterogeneity appears to be increased by chlorination of the phenyl ring.

Solenoid proteins are elongated tandem repeat proteins with diverse biological functions, making them attractive targets for protein design. Advances in machine learning have transformed our understanding of sequence-structure relationships, enabling new approaches for de novo protein design. Here, we present an in silico evolution platform that couples a solenoid discriminator network with AlphaFold2 as an oracle within a genetic algorithm. Starting from random sequences, we design α-, β-, and αβ-solenoid backbones, generating structures that span natural and novel solenoid space. We experimentally characterise 41 solenoid designs, with α-solenoids consistently folding as intended, including one structurally validated design that closely matches the design model. All β-solenoids initially failed, reflecting the difficulty of designing β-strand majority proteins. By introducing terminal capping elements and refining designs based on earlier experimental screens, we generate two β-solenoids that have biophysical properties consistent with their designs. Our approach achieves fold-specific hallucination-based design without depending on explicit structural templates.

The study of cycloaddition mechanisms is central to the fabrication of extended sp carbon nanostructures such as graphene nanoribbons and spin chains. Reaction modeling in this context has focused mostly on putative, energetically preferred, exothermic products with limited consideration for symmetry allowed or forbidden mechanistic effects. To classify and optimize allowed reaction mechanisms, modern topological tools can be explored. Here, we introduce a scheme for classifying symmetry-forbidden reaction coordinates in Woodward-Hoffmann correlation diagrams. We show that topological classifiers grant access to the study of reaction pathways and correlation diagrams in the same footing, for the purpose of elucidating mechanisms and products of polycyclic aromatic azomethine ylide (PAMY) cycloadditions of pentacene-yielding polycyclic aromatic hydrocarbons with an isoindole core in the solid-state and on surfaces, as characterized by mass spectrometry and scanning tunneling microscopy, respectively. By means of a tight-binding reaction model and broken-symmetry density functional theory (DFT), we find topologically-allowed pathways for an endothermic reaction mechanism. Our work unveils topological classification as a crucial element of reaction modeling for nanographene engineering, and highlights its fundamental role in the design of cycloadditions in on-surface and solid-state chemical reactions, while underscoring that exothermic pathways can be topologically-forbidden.

In March 2011, the Fukushima Daiichi Nuclear Power Station (FDNPS) suffered reactor core overheating and fuel melting following the Great East Japan Earthquake and tsunami, producing complex microparticles from vaporized and rapidly solidified nuclear and structural materials. The chemical states and local structures of key elements in these particles, particularly uranium and plutonium, remain poorly constrained. Here, we present the synchrotron-based micro-focused X-ray absorption fine structure (XAFS) and X-ray diffraction (XRD) study of microparticles recovered from inside Unit 2 of FDNPS. The particles contain uranium, zirconium, and trace plutonium uniformly incorporated into chemically homogeneous oxide matrices. Two types were identified: uranium-rich particles with cubic UO and mixed U-Zr oxides with tetragonal ZrO, the latter persisting at room temperature, indicating rapid cooling from a high-temperature metastable phase above 1650 °C. Both uranium and plutonium are mainly in the +4 state, with localized valence increases in zirconium-rich regions, suggesting redox-driven charge compensation during crystallization. These results provide direct evidence of melt evolution, actinide mixing, and oxidation-state preservation during severe reactor accidents, informing models of core degradation and strategies for safe decommissioning at FDNPS.

Antibiotic resistance is rapidly emerging as one of the most critical health threats, with resistant microorganisms progressively diminishing the effectiveness of established antibiotics. As a result, the development of therapeutic approaches that effectively target resistant pathogens is of utmost importance. In this study, we developed inhibitors for APH(2")-IVa, a bacterial kinase conveying resistance to aminoglycoside antibiotics. Starting from a hit of a fragment-based screening, we explored the inhibitory motif by structure-based design, ultimately leading to a series of triazole analogues. Advanced analogues displayed promising ADME properties, emerging selectivity vs a panel of human kinases, permeability in both Gram-positive and Gram-negative bacteria, and a moderate antibiotic efficacy for clinical strains of P. aeruginosa. Taken together, our results suggest inhibition of bacterial kinases could be a promising option to reinstall the efficacy of aminoglycoside antibiotics.

Given the promising prospect of nanozymes in colorimetric test strips, it is essential to eliminate the interferences of their multi-activities and various colors on the test strip. Here, white Mn-based metal-organic frameworks (Mn-MOFs) with ultrathin 2D morphology (3 nm thick) were successfully synthesized by a simple ultrasonic approach. The origin of the white optical property in Mn-MOFs was systematically investigated, revealing that it stems from specific metal-ligand coordination polymerization rather than morphological features or defect states. Mn-MOF nanozymes possessed exclusive peroxidase-mimicking activity rather than oxidase-like activity, effectively resisting O interference during colorimetric assay. Moreover, Mn-MOF nanozymes displayed unique substrate selectivity without additional modification. Unlike other colored nanozymes, the whiteness of Mn-MOF nanozymes enhanced the paper's whiteness, boosting contrast for colorimetric detection on test strip. This study pioneers a systematic investigation into the origin of whiteness in MOF nanozymes. The coordination-defined properties enable interference-free optical design and O-resistant on-site detection.

Langbeinite is proposed as a promising host matrix for radioactive wastes, but no structures incorporating actinides have been reported yet. In this work, a series of single crystals of CsULn(PO) (Ln = Ce - Nd and Sm - Lu), the first reported langbeinite-type structure incorporating actinides (U) which crystallizes in the cubic space group P23, have been successfully prepared by optimizing the high-temperature molten salt method. Their 3D frameworks are characterized by a typical langbeinite structure with U/Ln co-occupying six-coordinated octahedra and Cs cations filling closed large-sized cavities. The compounds exhibit high thermal stability up to 1200 °C under N and show outstanding leaching resistance, with the leaching rates of U and Nd at 10 g·m·d and Cs 10 g·m·d. This study highlights the potential of langbeinite-type structures for effectively immobilizing both tetravalent and trivalent actinides as promising waste forms.

According to the World Health Organization (WHO), antimicrobial resistance is a serious global health issue. Overcoming antibiotic resistance involves several strategies, including the inhibition of resistance mechanisms. Among the various resistance mechanisms, aminoglycoside phosphotransferases (APHs) catalyze the transfer of the γ-phosphate from a nucleotide donor to various aminoglycosides, leading to their inactivation. In this work, using a fragment-based drug design (FBDD) approach, we have identified and characterized a promising APH inhibitor capable of increasing the sensitivity of Pseudomonas aeruginosa and Staphylococcus aureus resistant to aminoglycosides. It is therefore a good candidate for the future development of APH inhibitors to be prescribed in combination with aminoglycosides. This molecule is a competitive inhibitor of adenosine 5'-triphosphate (ATP), the phosphate donor of APHs. Further studies are required to optimize this molecule to improve its specificity for APHs and its bioavailability in bacteria.

α-Synuclein condensates can mature into amyloid fibrils, demonstrating a link between phase separation and amyloid aggregation. However, the mechanisms driving this maturation are not fully understood, particularly in the context of pathological post-translational modifications that modulate α-synuclein amyloid aggregation. Although often studied in isolation, condensates appear to interact with surfaces in vitro and in the cell. Notably, the N-terminus of α-synuclein is implicated in membrane binding and may influence condensate-surface interactions. Here, we developed a microscopy-based protocol to investigate how N-terminal truncation affects α-synuclein condensate formation, surface wetting, and maturation. We found that N-terminal truncation enhances condensate wettability and accelerates maturation. Conversely, perturbing condensate-surface interactions reduces condensate wettability and delays maturation. These results suggest that enhanced wettability promotes condensate maturation, likely by increasing condensate surface-to-volume ratios. Our findings reveal distinct mechanistic roles for the N-terminus of α-synuclein and highlight condensate wettability and interfacial dynamics as key modulators of aggregate formation.

Synchrotron radiation provides exceptional sensitivity and resolution, enabling the acquisition of highly precise information critical for advancing fuel cell technology. When combined with machine learning-based, data-driven approaches, it offers powerful insights into reaction pathways and is poised to significantly accelerate the discovery of next-generation fuel cell catalysts. However, the singular characterization and complex feature space of synchrotron radiation data, necessitates a novel approach to obtain structural insights into the fuel cell catalyst. In this work, we propose a novel framework for rational electrocatalyst discovery that integrates machine learning with multimodal spectral descriptors derived from advanced synchrotron radiation techniques-XANES, EXAFS, XRD, SAXS, PDF, and HAXPES (Pt3d, Pt4f, and VB). We employed structure-performance prediction machine learning model to identify key multimodality descriptors. By assessing the importance of these modalities, we established a reverse-engineering framework for catalyst discovery, enabling the structural inference of new high-performance catalyst candidates. The experimentally derived descriptor space was validated through physics-based theoretical modelling, effectively narrowing the pool of potential candidates, and enabling the precise identification of the optimal structure-performance electrocatalyst. The proposed framework enables a shift, beyond empirical catalyst screening, toward a more efficient, interpretable, and high-throughput strategy for the discovery and design of next-generation electrocatalysts.

Inorganic nanoparticles (NPs) have significant potential for various applications; however, achieving stable dispersion in organic media and polymers remains a key challenge for their industrial use. We developed a novel dispersant, tributyl(3-((3,4-dihydroxyphenylamino)-3-oxopropyl)phosphonium chloride) (TPC), which contains a catechol group for strong NPs binding and a phosphonium chloride moiety for effective dispersion. The versatility of TPC was demonstrated by stabilizing TiO₂, Fe₂O₃, and ZnO NPs in methanol using bead milling, as confirmed by TGA, DLS, zeta potential, and TEM analyses. In addition, TPC exhibited broad compatibility across solvents with varying dielectric constants. Furthermore, several hybrid polymer films were prepared by casting and photosolidification from monomers to assess their dispersibility and TPC-polymer matrix interactions, using Cole-Cole plots. Notably, poly(D,L-lactic acid) hybrid films retained their dispersion stability after recycling, highlighting the sustainability of TPC-coated NPs for material design. This study presents the first integration of phosphonium cations with catechol groups as dispersants, offering not only a breakthrough approach for developing nanocomposite materials with superior stability and performance, but also establishing a versatile platform concept that introduces a new design principle for universal and sustainable dispersant development across diverse nanomaterials and polymer systems.

Although chirality-mirror asymmetry-underpins biomolecular interactions, difficulties in quantifying it have long obscured insight into the precise role it plays in these interactions. Two standard chirality measures are the pseudoscalar Osipov-Pickup-Dunmur (OPD) index, which yields an asymmetry index with a sign, and the Hausdorff Chirality Measure (HCM), which yields only a magnitude. Theoretical arguments have shown that OPD is expected to have "chiral zeros," which occur when a chiral object is incorrectly assigned a chirality index value of zero. However, their existence remains theoretical and their abundance in real (bio)molecules has not been studied. We examined the differences between OPD and HCM in four different biological systems representing several different scales of chirality and found chiral zeros to be prevalent in each of these cases. Thus, we conclude that OPD is unsuitable for the quantification of chirality of complex molecular structures except in simple cases of helicoids with singular degrees of freedom for their reconfiguration. HCM also gave a weak correlation with biological properties. Altogether our findings indicate that new mathematical approaches to differentiate opposite handed chiral structures are needed especially considering the rapid prolifiration of machine learning and artificial intelligence algorithms for biochemistry and structural biology.

FET (FUS-EWSR1-TAF15) family proteins form mesoscale clusters under physiological conditions at concentrations well below the threshold for phase separation. However, how ATP, an amphiphilic molecule and essential cellular metabolite, affects this clustering remains unclear. Here, I show that ATP modulates the size of subsaturation mesoscale clusters in a concentration-dependent manner. At low concentrations (1-2 mM), ATP promotes clustering by acting as a molecular crosslinker, leading to larger assemblies. At a moderate concentration (5 mM), clusters become smaller but remain stable, whereas at a higher concentration (10 mM), the cluster size is reduced. Other amphiphilic molecules, including sodium xylene sulfonate, sodium toluene sulfonate, and hexanediol, display comparable concentration-dependent effects. These observations cannot be explained solely by hydrotropic or kosmotropic mechanisms; instead, they arise from non-specific interactions between amphiphilic molecules and protein. Thus, the intrinsic chemical features of small molecules and FET proteins collectively govern mesoscale clustering at subsaturation concentrations.

Petroleum-based plastics have raised global concerns in recent years. Degradable bio-based supramolecular plastics (SPs), coupled with eco-friendly hydroplastic processing, become sustainable alternatives. However, the inherent contradiction between hydroplastic processability and water-resistance restricts their applications in humid environments. Here, we report a cascade strategy of pre-hydroplastic processing and post-noncovalent crosslinking to stepwise achieve hydroplastic processing and water-resistance of alginate SPs. Alginate-cetyltrimethylammonium (SA-CTAB) SPs are firstly processed into various two-dimensional/three-dimensional shapes due to the excellent hydroplasticity. Then, Ca ions are introduced to improve the mechanical strength, water-resistance, and flame retardancy by forming robust crosslinks with alginate chains. The wet tensile strength and Young's modulus of the obtained SA-CTAB-Ca SPs are respectively enhanced for 38 times to 15 MPa and 110 times to 0.57 GPa after crosslinking, which will substantially broaden their applicability in humid environments. We expect this work will provide a sustainable processing route for high-performance alginate SPs.

The development of new methods for forming carbon-carbon bonds is essential for advancing the synthesis of biologically active molecules. Achieving high selectivity in these reactions remains a significant challenge in organic chemistry. Here we show that a nickel-catalyzed β-arylation and benzylation of 2'-hydroxychalcones enables the efficient synthesis of chalcone derivatives. This transformation is directed by the substrate's intrinsic hydroxy group, resulting in high chemoselectivity and avoiding unwanted byproducts. The resulting chalcone derivatives can be converted in one step into a series of 3-functionalized 4-hydroxycoumarin compounds. These compounds demonstrate excellent anticoagulant effects in animal studies, with some showing greater activity than the widely used drug warfarin. This approach offers a promising strategy for developing therapeutic agents and functional materials based on the chalcone structure.

In industry phenolic wastewaters are generated at high temperature and required for cooling before post-treatment. The utilization of thermal energy for the treatment of phenolic wastewaters is often overlooked. Herein, we utilize thermophilic MoNO nanozyme for highly efficient degradation of phenolic pollutants at high temperature. Both the laccase-like and peroxidase-like activities of MoNO nanozyme increase with the temperature up to 90 °C. The efficiency of phenol oxidation at 60 °C is about 3-fold of that at 25 °C. Phenol is mineralized into CO and HO, the removal of total organic carbon by MoNO + HO is 97.0 ± 0.2% at 60 °C within 20 min. Moreover, MoNO nanozyme can also degrade other phenolic pollutants such as 2,4-dichlorophenol, pyrocatechol, 4-aminophenol and o-nitrophenol. The catalytic mechanism and phenol degradation route are also analyzed. This work provides a promising strategy for highly efficient treatment of phenolic wastewaters in an energy-saving way.

Self-driving labs (SDLs) combine robotic automation with artificial intelligence (AI) to allow autonomous, high-throughput experimentation. However, robot manipulation in most SDL workflows operates in an open-loop manner, lacking real-time error detection and error correction. This can reduce reliability and overall efficiency. Here, we introduce LIRA (Localization, Inspection, and Reasoning), which is an edge computing module that enhances robotic decision-making through vision-language models (VLMs). LIRA enables precise localization, automated error inspection, and reasoning, thus allowing robots to adapt dynamically to variations from the expected workflow state. Integrated within a client-server framework, LIRA supports remote vision inspection and seamless multi-platform communication, improving workflow flexibility. Through extensive testing, LIRA achieves high localization accuracy, a tenfold reduction in localization time, and real-time inspection across diverse tasks, increasing the efficiency and robustness of autonomous workflows considerably. As an open-source solution, LIRA facilitates AI-driven automation in SDLs, advancing autonomous, intelligent, and resilient laboratory environments. Longer term, this will accelerate scientific discoveries through more seamless human-machine collaboration.

In-situ generation of a hydrogelator from non-assembling precursors offers an effective strategy for preparing supramolecular hydrogel materials with precise spatiotemporal control. These hydrogels hold broad potential for applications ranging from theranostics to chemical sensing. Herein, we report a method for the in-situ formation of a coumarin-based supramolecular hydrogelator by simply mixing aqueous solutions of two non-assembling precursors under ambient conditions. The formation of the hydrogelator, its subsequent self-assembly into a hydrogel network, and the resulting material properties can all be modulated via acid catalysis. The hydrogelator exhibits excellent selectivity toward Fe(II) ions, providing a distinct colorimetric response with a linear correlation and a notable detection limit. Additionally, the hydrogel material can be easily applied to disposable paper strips, enabling convenient and portable detection of Fe(II) ions. This system demonstrates strong potential for addressing key challenges in Fe(II) ion sensing in both aqueous environments and self-assembled hydrogel states.

Photomechanical bending or mechanical flexibility in single crystals is an interesting landscape for innovative technological applications, including smart medical devices, molecular machines, artificial muscles, microrobots, and flexible electronic actuators. However, metal-organic crystals with multiple dynamic effects such as bending (in-situ), jumping, fracturing, and splitting in the absence of mechanical energy or temperature is interesting and relatively unexplored. The development of these materials presents significant challenges, requiring a thorough grasp of the underlying mechanisms for practical applications. Herein, we developed a Zn based 1D coordination polymer (CP) crystal {[Zn(DCTP)(4-nvp)]·(CHOH)} (1) {HDCTP = 2,5-dichloroterephthalic acid; 4-nvp = 4-(1-naphthylvinyl)pyridine} which undergoes [2 + 2] cycloaddition under both UV irradiation and sunlight to generate a partially dimerized product of a two-dimensional coordination polymer (2D CP) [Zn(DCTP)(rctt-4-pncb)] (i1). During UV irradiation, these single crystals exhibit photomechanical effects like jumping, bending, cracking, and swelling to relieve anisotropic strain from the light. Surprisingly, bent-shaped single crystals (1b) identical in structure to 1 were also obtained in-situ without any external stimuli, simply by keeping reaction mixture for an extended period. A time-resolved photocrystallographic study fully described the photoinduced structural transformation. Nanoindentation measurements complemented a DFT study of mechanical property trends for irradiated and bent Zn-based photosalient crystals.

Superwetting separation membranes (SWMs), renowned for their low energy consumption, high efficiency, and high flux in liquid mixture separation, hold promising application prospects across industries such as chemical processing, resource utilization, and environmental remediation. Liquid-liquid separation is an indispensable operation across diverse chemical industries. This perspective highlights recent advances in SWMs for liquid-liquid separation, focusing on mechanisms across immiscible, partially miscible, and fully miscible systems. Immiscible separation relies on tuning membrane surface energy and pore structure, while miscible systems require synergistic control of molecular interactions among solid membranes, inductive agents, and target components. Integration with conventional membrane technologies has enabled innovative module designs to enhance separation efficiency. The perspective provides insights into fundamental mechanisms, optimization strategies, and challenges in transitioning SWMs from lab-scale research to industrial applications. Emphasis is placed on bridging material innovation with scalable fabrication and system integration to accelerate practical implementation in complex separation scenarios.

Histidine phosphorylation is a non-canonical post-translational modification (PTM), with 1-phosphohistidine (1-pHis) and 3-phosphohistidine (3-pHis) isoforms, that is understudied due to a lack of robust reagents, including high-affinity pHis-specific antibodies. Engineering pHis antibodies is challenging due to the labile nature of its phosphoramidate (P-N) bond. We developed a strategy for in vitro engineering of antibodies for the detection of native 3-pHis targets, in which the rabbit SC44-8 anti-3-pTza mAb is humanized into a scaffold (hSC44) that is suitable for phage display. Six unique Fab phage-displayed hSC44 scaffold libraries were screened for antibodies that bound 3-pHis with higher affinity and had specificity for 3-pHis versus 3-pTza. hSC44.20N32F, the best engineered antibody, has ~10-fold higher affinity for 3-pHis than parental hSC44. Eleven new Fab structures, including the first antibody-pHis peptide structures, together with structural and quantum mechanical calculations, provided molecular insights into 3-pHis and 3-pTza discrimination by hSC44.20N32F and the increased affinity obtained through engineering. We demonstrated the utility of these high-affinity 3-pHis-specific antibodies for the recognition of pHis proteins in mammalian cells by immunoblotting and immunofluorescence staining. Our work describes a general method for engineering labile PTM-specific antibodies and provides novel antibodies for investigating the role of 3-pHis in cell biology.